Skip to main content
NCBI home page
British Heart Journal logoLink to British Heart Journal
. 1985 Oct;54(4):405–414. doi: 10.1136/hrt.54.4.405

Controlled trial of enalapril in congestive cardiac failure.

B P McGrath, L Arnolda, P G Matthews, B Jackson, G Jennings, H Kiat, C I Johnston
PMCID: PMC481919  PMID: 2996575

Abstract

Twenty five patients with chronic congestive cardiac failure had enalapril (n = 13) or placebo (n = 12) added to their existing regimen of digoxin and frusemide in a randomised double blind trial. Four hours after the first 5 mg dose, the enalapril group showed significant falls in blood pressure, heart rate, and concentrations of plasma angiotensin II, angiotensin converting enzyme, and noradrenaline. During the 12 week trial heart failure became worse in one enalapril treated patient (8%) and in seven placebo treated patients (58%). There were no significant changes in cardiac ejection fraction or exercise duration in either group. Plasma noradrenaline response to graded exercise and maximum exercise rate-pressure product were significantly reduced after four and 12 weeks of active treatment but unchanged with placebo treatment. There was a sustained increase in plasma potassium and a slight rise in plasma creatinine in the enalapril group. Plasma concentrations of the active drug, enalaprilate, were dose related and log enalaprilate correlated significantly with percentage of plasma angiotensin converting enzyme activity (r = -0.66). Enalapril was well tolerated and produced no adverse effects. The drug appears to be superior to placebo and offers considerable promise for the treatment of this condition.

Full text

PDF
405

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ader R., Chatterjee K., Ports T., Brundage B., Hiramatsu B., Parmley W. Immediate and sustained hemodynamic and clinical improvement in chronic heart failure by an oral angiotensin-converting enzyme inhibitor. Circulation. 1980 May;61(5):931–937. doi: 10.1161/01.cir.61.5.931. [DOI] [PubMed] [Google Scholar]
  2. Amsterdam E. A., Mason D. T. Exercise testing and indirect assessment of myocardial oxygen consumption in evaluation of angina pectoris. Cardiology. 1977;62(3):174–189. doi: 10.1159/000169852. [DOI] [PubMed] [Google Scholar]
  3. Arnold S. B., Williams R. L., Ports T. A., Baughman R. A., Benet L. Z., Parmley W. W., Chatterjee K. Attenuation of prazosin effect on cardiac output in chronic heart failure. Ann Intern Med. 1979 Sep;91(3):345–349. doi: 10.7326/0003-4819-91-3-345. [DOI] [PubMed] [Google Scholar]
  4. Awan N. A., Evenson M. K., Needham K. E., Win A., Mason D. T. Efficacy of oral angiotensin-converting enzyme inhibition with captopril therapy in severe chronic normotensive congestive heart failure. Am Heart J. 1981 Jan;101(1):22–31. doi: 10.1016/0002-8703(81)90379-3. [DOI] [PubMed] [Google Scholar]
  5. Awan N. A., Mason D. T. Vasodilator therapy of severe congestive heart failure: the special importance of angiotensin-converting enzyme inhibition with captopril. Am Heart J. 1982 Nov;104(5 Pt 2):1127–1136. doi: 10.1016/0002-8703(82)90041-2. [DOI] [PubMed] [Google Scholar]
  6. Blythe W. B. Captopril and renal autoregulation. N Engl J Med. 1983 Feb 17;308(7):390–391. doi: 10.1056/NEJM198302173080709. [DOI] [PubMed] [Google Scholar]
  7. Boyd G. W., Landon J., Peart W. S. The radioimmunoassay of angiotensin II. Proc R Soc Lond B Biol Sci. 1969 Jul 1;173(1032):327–338. doi: 10.1098/rspb.1969.0058. [DOI] [PubMed] [Google Scholar]
  8. Cody R. J. The effect of captopril on postural hemodynamics and autonomic responses in chronic heart failure. Am Heart J. 1982 Nov;104(5 Pt 2):1190–1196. doi: 10.1016/0002-8703(82)90050-3. [DOI] [PubMed] [Google Scholar]
  9. Cushman D. W., Cheung H. S. Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung. Biochem Pharmacol. 1971 Jul;20(7):1637–1648. doi: 10.1016/0006-2952(71)90292-9. [DOI] [PubMed] [Google Scholar]
  10. Davis R., Ribner H. S., Keung E., Sonnenblick E. H., LeJemtel T. H. Treatment of chronic congestive heart failure with captopril, an oral inhibitor of angiotensin-converting enzyme. N Engl J Med. 1979 Jul 19;301(3):117–121. doi: 10.1056/NEJM197907193010301. [DOI] [PubMed] [Google Scholar]
  11. Dzau V. J., Colucci W. S., Williams G. H., Curfman G., Meggs L., Hollenberg N. K. Sustained effectiveness of converting-enzyme inhibition in patients with severe congestive heart failure. N Engl J Med. 1980 Jun 19;302(25):1373–1379. doi: 10.1056/NEJM198006193022501. [DOI] [PubMed] [Google Scholar]
  12. Fitzpatrick D., Nicholls M. G., Ikram H., Espiner E. A. Haemodynamic, hormonal, and electrolyte effects of enalapril in heart failure. Br Heart J. 1983 Aug;50(2):163–169. doi: 10.1136/hrt.50.2.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fortuin N. J., Hood W. P., Jr, Craige E. Evaluation of left ventricular function by echocardiography. Circulation. 1972 Jul;46(1):26–35. doi: 10.1161/01.cir.46.1.26. [DOI] [PubMed] [Google Scholar]
  14. Francis G. S., Goldsmith S. R., Ziesche S. M., Cohn J. N. Response of plasma norepinephrine and epinephrine to dynamic exercise in patients with congestive heart failure. Am J Cardiol. 1982 Apr 1;49(5):1152–1156. doi: 10.1016/0002-9149(82)90039-x. [DOI] [PubMed] [Google Scholar]
  15. Gavras H., Faxon D. P., Berkoben J., Brunner H. R., Ryan T. J. Angiotensin converting enzyme inhibition in patients with congestive heart failure. Circulation. 1978 Nov;58(5):770–776. doi: 10.1161/01.cir.58.5.770. [DOI] [PubMed] [Google Scholar]
  16. Hansen J. F., Christensen N. J., Hesse B. Determinants of coronary sinus noradrenaline in patients with ischaemic heart disease: coronary sinus catecholamine concentration in relation to arterial catecholamine concentration, pulmonary artery oxygen saturation and left ventricular end-diastolic pressure. Cardiovasc Res. 1978 Jul;12(7):415–421. doi: 10.1093/cvr/12.7.415. [DOI] [PubMed] [Google Scholar]
  17. Hricik D. E., Browning P. J., Kopelman R., Goorno W. E., Madias N. E., Dzau V. J. Captopril-induced functional renal insufficiency in patients with bilateral renal-artery stenoses or renal-artery stenosis in a solitary kidney. N Engl J Med. 1983 Feb 17;308(7):373–376. doi: 10.1056/NEJM198302173080706. [DOI] [PubMed] [Google Scholar]
  18. Hörtnagl H., Benedict C. R., Grahame-Smith D. G. A sensitive radioenzymatic assay for adrenaline and noradrenaline in plasma. Br J Clin Pharmacol. 1977 Oct;4(5):553–558. doi: 10.1111/j.1365-2125.1977.tb00785.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johnston C. I., Jackson B., McGrath B., Matthews G., Arnolda L. Relationship of antihypertensive effect of enalapril to serum MK-422 levels and angiotensin converting enzyme inhibition. J Hypertens Suppl. 1983 Oct;1(1):71–75. [PubMed] [Google Scholar]
  20. Johnston C. I., Millar J. A., McGrath B. P., Matthews P. G. Long-term effects of captopril (SQ14 225) on blood-pressure and hormone levels in essential hypertension. Lancet. 1979 Sep 8;2(8141):493–496. doi: 10.1016/s0140-6736(79)91552-6. [DOI] [PubMed] [Google Scholar]
  21. Kalff V., Kelly M. J., Jennings G. L., Lim Y. L., Anderson S. T., Korner P. I., Harper R. W., Pitt A. The radionuclide assessment of left ventricular function using graded exercise in normal subjects. Aust N Z J Med. 1980 Oct;10(5):533–539. doi: 10.1111/j.1445-5994.1980.tb04972.x. [DOI] [PubMed] [Google Scholar]
  22. Levine T. B., Franciosa J. A., Cohn J. N. Acute and long-term response to an oral converting-enzyme inhibitor, captopril, in congestive heart failure. Circulation. 1980 Jul;62(1):35–41. doi: 10.1161/01.cir.62.1.35. [DOI] [PubMed] [Google Scholar]
  23. McGrath B. P., Denham I. M., Johnston C. I. Clinical improvement and hormonal changes in severe cardiac failure after captopril treatment. Aust N Z J Med. 1981 Dec;11(6):639–644. doi: 10.1111/j.1445-5994.1981.tb03538.x. [DOI] [PubMed] [Google Scholar]
  24. Packer M., Medina N., Yushak M. Contrasting hemodynamic responses in severe heart failure: comparison of captopril and other vasodilator drugs. Am Heart J. 1982 Nov;104(5 Pt 2):1215–1223. doi: 10.1016/0002-8703(82)90054-0. [DOI] [PubMed] [Google Scholar]
  25. Packer M., Meller J., Medina N., Yushak M., Gorlin R. Hemodynamic characterization of tolerance to long-term hydralazine therapy in severe chronic heart failure. N Engl J Med. 1982 Jan 14;306(2):57–62. doi: 10.1056/NEJM198201143060201. [DOI] [PubMed] [Google Scholar]
  26. Sharpe D. N., Douglas J. E., Coxon R. J., Long B. Low-dose captopril in chronic heart failure: acute haemodynamic effects and long-term treatment. Lancet. 1980 Nov 29;2(8205):1154–1157. doi: 10.1016/s0140-6736(80)92593-3. [DOI] [PubMed] [Google Scholar]
  27. Sharpe D. N., Murphy J., Coxon R., Hannan S. F. Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study. Circulation. 1984 Aug;70(2):271–278. doi: 10.1161/01.cir.70.2.271. [DOI] [PubMed] [Google Scholar]
  28. Thomas J. A., Marks B. H. Plasma norepinephrine in congestive heart failure. Am J Cardiol. 1978 Feb;41(2):233–243. doi: 10.1016/0002-9149(78)90162-5. [DOI] [PubMed] [Google Scholar]
  29. Turini G. A., Brunner H. R., Gribic M., Waeber B., Gavras H. Improvement of chronic congestive heart-failure by oral captopril. Lancet. 1979 Jun 9;1(8128):1213–1215. doi: 10.1016/s0140-6736(79)91897-x. [DOI] [PubMed] [Google Scholar]
  30. Ulm E. H., Hichens M., Gomez H. J., Till A. E., Hand E., Vassil T. C., Biollaz J., Brunner H. R., Schelling J. L. Enalapril maleate and a lysine analogue (MK-521): disposition in man. Br J Clin Pharmacol. 1982 Sep;14(3):357–362. doi: 10.1111/j.1365-2125.1982.tb01991.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Walsh W. F., Greenberg B. H. Results of long-term vasodilator therapy in patients with refractory congestive heart failure. Circulation. 1981 Sep;64(3):499–505. doi: 10.1161/01.cir.64.3.499. [DOI] [PubMed] [Google Scholar]

Articles from British Heart Journal are provided here courtesy of BMJ Publishing Group

RESOURCES